IVGTT derived Metabolic Flexibility measures in Adults with Pre-Diabetes: Association with Insulin Sensitivity and Gender Differences

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 780-806-Determinants of Insulin Resistance & Associated Metabolic Disturbances
Basic/Translational
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-787
Lucy W Piner1, Hiba Najib Abou Assi*2, Cris A Slentz1, Catherine Mikus1, Lorraine Elliott Penry1 and William E Kraus1
1Duke University Medical Center, 2Duke University Medical Center, Durham, NC
Metabolic Flexibility generally refers to the capacity to adapt fuel oxidation to fuel availability and has been measured as alterations in Respiratory Exchange Ratio (RER), which serves as a representation for substrate oxidation and ranges from 0.70 for fat oxidation to 1.00 for total carbohydrate oxidation.   Metabolic Flexibility is thought to be impaired in insulin resistant states.  The purpose of this study was to determine whether measures of insulin sensitivity are associated with metabolic flexibility among adults with prediabetes.  Methods:  We used indirect calorimetry to estimate energy expenditure (EE) as well as the relative contribution of fat and carbohydrate to EE (respiratory exchange ratio; RER) at rest (fasting conditions) and during an intravenous glucose tolerance test (IVGTT) in 127 sedentary, overweight (BMI 25-35 kg.m2), adults (45-70 y) with pre-diabetes (fasting glucose 95-125mg/dL).  We then calculated the magnitude of change (Δ) in RER in response to glucose (ΔRERg) and insulin (ΔRERi) injections during the IVGTT.  Results:  Fasting RER was lower in females than males (0.804 vs 0.817, p<0.05).  After controlling for fasting RER, ΔRERi was greater (0.122 vs 0.099, p<0.01) in females than males.  There were significant positive correlations between ΔRERi and insulin sensitivity assessed by IVGTT (Si; Spearman Rho r=0.23, p=0.03) and by OGTT (Mastuda insulin sensitivity index; r=0.32, p<0.001). There were also significant inverse correlations between ΔRERi and fasting glucose (r=-0.22, p<0.05), fasting insulin (r=-0.31, p<0.001), and HOMA-IR (r=-0.32, p<0.001).  There were no significant correlations between ΔRERg and any of these measures.  Conclusion:  Our data indicate that women with prediabetes oxidize a greater proportion of fat than men under fasting conditions.  Women with prediabetes also appear to be more metabolically flexible.  Our findings also indicate that insulin sensitivity is associated with a greater degree of metabolic flexibility (the ability to shift from fat to carbohydrate oxidation, during the insulin phase of the IVGTT).  The correlations between insulin sensitivity and the magnitude of change in RER response to the insulin infusion, but not the glucose infusion, indicate that in adults with prediabetes, improving  peripheral insulin resistance at the level of the skeletal muscles, may lead to improved metabolic flexibility and fuel utilization.

Nothing to Disclose: LWP, HNA, CAS, CM, LEP, WEK

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